Challenges in Mucosal HIV Vaccine Development: Lessons from Non-Human Primate Models

Abstract

An efficacious HIV vaccine is urgently needed to curb the AIDS pandemic. The modest protection elicited in the phase III clinical vaccine trial in Thailand provided hope that this goal might be achieved. However, new approaches are necessary for further advances. As HIV is transmitted primarily across mucosal surfaces, development of immunity at these sites is critical, but few clinical vaccine trials have targeted these sites or assessed vaccine-elicited mucosal immune responses. Pre-clinical studies in non-human primate models have facilitated progress in mucosal vaccine development by evaluating candidate vaccine approaches, developing methodologies for collecting and assessing mucosal samples, and providing clues to immune correlates of protective immunity for further investigation. In this review we have focused on non-human primate studies which have provided important information for future design of vaccine strategies, targeting of mucosal inductive sites, and assessment of mucosal immunity. Knowledge gained in these studies will inform mucosal vaccine design and evaluation in human clinical trials.

Localized cyclical variations in immunoproteins in the female genital tract and the implications on the design and assessment of mucosal infection and therapies

“…There is currently a need to design and evaluate vaccines that are capable of eliciting protective mucosal immunological responses that can prevent HIV acquisition and transmission, particularly in women who have been reported to be more susceptible to infection compared to age‐matched males . Indeed, a number of studies have evaluated aspects of this approach such as the linkage between the nasal and genital mucosal compartments, and the quality of the responses that are elicited by various antigens and delivery methods .…”

Pharmaceutical Approaches to HIV Treatment and Prevention

“…[163] Mucosa-associated lymphoid tissue (MALT) are the sites where mucosal vaccines can be administered, as this tissue is functionally connected throughout the body. [163] For instance, nasalassociated lymphoid tissue and gut-associated lymphoid tissue are potential sites for induction. However, not all sites provide the same immunity, due to unique local environments of the mucosa.…”

“…These correlates involve both the cellular and humoral arms of the immune system, so the mechanism is not fully clear. [163] NHP and other models have been used to study mucosal vaccines and have shown some success. One study in sheep showed successful elicitation of high levels of antigen-specific mucosal IgA and large amounts of local antigen-reactive B cells after intramuscular injection and prolonged intravaginal administration (via ring) of 167 μg of both CN54gp140 protein and R848 adjuvant.…”

“…Mucosal vaccines have been explored, but thus far have not been shown to work better than systematic vaccines. It is thought that a combination of a systematic and mucosal vaccine may result in increased protection compared to either one alone . Mucosa‐associated lymphoid tissue (MALT) are the sites where mucosal vaccines can be administered, as this tissue is functionally connected throughout the body .…”

Harnessing T Follicular Helper Cell Responses for HIV Vaccine Development

“…immunization are not known [ 132 ]. Mucosal immunization routes (e.g., oral, intranasal, intratracheal, intrarectal, and intravaginal) have shown some success in NHP studies but have failed thus far in human HIV-vaccine trials (reviewed in [ 116 ]). Further studies will show whether mucosal vaccination alone or in combination with systemic immunization will serve as a strategy to induce protective immune responses against HIV in humans.…”